A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity

Qu, Yueyang; Fan, Ailong; Luo, Yong; Lu, Yao; Liu, Tingjiao; Zhao, Weijie; Lin, Baiquan

doi:10.1016/j.biomaterials.2017.11.010

Cited by 72 publications

(54 citation statements)

References 25 publications

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“…Thus, tissue culture is a better choice to reconstitute the chemokine microenvironment of an organ. Cell culture‐based liver‐on‐a‐chip and kidney‐on‐a‐chip have been reported previously . A microfluidically linked kidney‐on‐a‐chip and liver‐on‐a‐chip was developed to identify organ–organ interactions in response to chemical toxicants .…”

Section: Discussionmentioning

confidence: 99%

“…Another advantage of microfluidic technique is that microfabricated culture systems create a microenvironment similar to conditions in vivo. Currently, microfluidic “organ‐on‐a‐chip” or “multi‐organs‐on‐a‐chip” is developed based on cell culture . However, the chemokine microenvironment of different organs is difficult to reproduce with cell culture‐based “organ‐on‐a‐chip” because these biomimetic systems do not contain all cell types in their natural architecture and the organ‐specific ECM.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Tissue‐Based Liver–Kidney‐on‐a‐Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

Tian

Pang

Qin

et al. 2019

Biotechnology Journal

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Extracellular vesicles (EVs) from cancer cells remodel distant organs to promote metastasis in vivo. A biomimetic microsystem may compensate costly and time-consuming animal models to accelerate the study of EV organotropism. A tissue-based liver-kidney-on-a-chip is developed with precision-cut tissue slices (PTSs) cultured to represent individual organs. The organotropism of breast cancer EVs is modeled using the biomimetic microsystem. A traditional animal model of EV organotropism is used to investigate the physiological similarity of the microfluidic model to animal models. It is demonstrated that breast cancer EVs show strong liver tropism rather than kidney tropism on both the microfluidic and animal models. It isfound that the metastatic inhibitor AMD3100 inhibits liver tropism effectively in both the microfluidic and animal models. Overall, the tropism of EVs to different organs is reconstituted on the microfluidic model. The liver-kidney-on-a-chip may expand the capabilities of traditional cell culture models and provide a faster alternative to animal models for EV studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Tissue‐Based Liver–Kidney‐on‐a‐Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

Tian

Pang

Qin

et al. 2019

Biotechnology Journal

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“…Qin et al [85] cultured primary rat glomerular endothelial cells (GECs) on a microfluidic chip to simulate the selective permeability of the renal barrier and then studied the cadmium-induced nephrotoxicity by detecting the expression of ZO-1 protein by GECs. Qu et al [86] have constructed a microfluidic platform that mimics nephrons, and the device contains glomerulus, Bowman's capsule, proximal renal lumen, and capillary tubules ( Figure 2C). Cisplatin and doxorubicin were added to the "renal blood flow" containing bovine serum albumin, E-cadherin, and vascular endothelial growth factor (VEGF), and other biomarkers were used to record the damage of a variety of primary kidney cells through fluorescence imaging.…”

Section: Kidney-on-a-chip For Drug Nephrotoxicity Testingmentioning

confidence: 99%

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Han

Wang

et al. 2020

Micromachines

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Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

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“…Two groups of DDP concentration (0, 20, 40, 60, and 80 μm/L and 0, 20, 40, 60, and 80 μm/L) and Cim (1 mm/L) were injected into the top chamber to verify the function of Cim for reducing DDP-induced toxicity. The doses were picked from the literature 41,42 . We compared the drug-induced nephrotoxicity of the Petri dishes (static) and microfluidic kidney chips (fluidic) by cell morphology, live/dead staining, and CCK-8 assay.…”

Section: Immunofluorescence Staining Fluorescence Images Of Live Celmentioning

confidence: 99%

Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip

Yin

Zhang

et al. 2020

Sci Rep

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The function and susceptibility of various drugs are tested with renal proximal tubular epithelial cells; yet, replicating the morphology and kidneys function using the currently available in vitro models remains difficult. To overcome this difficulty, in the study presented in this paper, a device and a threelayer microfluidic chip were developed, which provides a simulated environment for kidney organs. This device includes two parts: (1) microfluidic drug concentration gradient generator and (2) a flowtemperature controlled platform for culturing of kidney cells. In chip study, renal proximal tubular epithelial cells (RPTECs) and peritubular capillary endothelial cells (PCECs) were screened with the drugs to assess the drug-induced nephrotoxicity. Unlike cells cultured in petri dishes, cells cultured in the microfluidic device exhibited higher performance in terms of both cell growth and drug nephrotoxicity evaluation. It is worth mentioning that a significant decrease in cisplatin-induced nephrotoxicity was found because of the intervention of cimetidine in the microfluidic device. In conclusion, the different in the cell performance between the microfluidic device and the petri dishes demonstrates the physiological relevance of the nephrotoxicity screening technology along with the microfluidic device developed in this study. Furthermore, this technology can also facilitate the development of reliable kidney drugs and serve as a useful and efficient test-bed for further investigation of the drug nephrotoxicity evaluation.

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A nephron model for study of drug-induced acute kidney injury and assessment of drug-induced nephrotoxicity

Cited by 72 publications

References 25 publications

A Novel Tissue‐Based Liver–Kidney‐on‐a‐Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

A Novel Tissue‐Based Liver–Kidney‐on‐a‐Chip Can Mimic Liver Tropism of Extracellular Vesicles Derived from Breast Cancer Cells

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Efficient Drug Screening and Nephrotoxicity Assessment on Co-culture Microfluidic Kidney Chip

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